ROLE OF SOME VASCULAR ENDOTHELIUM- DERIVED VASOCONSTRICTOR AND VASODILATOR HYPERTENSION FACTORS lN THE PATHOGENESIS OF PORTAL

Abstract

Portal hypertension is one of the most serious complications of chronic liver diseases. It manifests clinically as ascites, splenomegaly, variceal bleeding and porto- systemic encephalopathy. Several factors have been attributed in the pathogenesis of portal hypertension. The endothelimn has emerged as an important modulator of vascular tone through the synthesis of various vasodilator and vasoconstrictor substances that have effects on the vascular tone. A munber of vasoactive substances have been advanced as potential mediators of intrahepatic portal hypertension. Recently, it has been realized that sinusoidal flow may be regulated by the hepatic stellate cells. Two vasoregulatory compounds with evident effects on these l ells include endothelin and nitric oxide, so they have been implicated in the pathogenesis and treatment of portal hypertension. Endothelins have been recogniz;ed as one of the most potent vasoconstrictors so far known, it has been demonstrated to cause sinusoidal constriction and portal hypertension in animal models. Inspite of that, serum endothelin levels in several studies have been contradictory. Nitric oxide is a powerful vasodilator endogenously released from

the vascular endothelimn. It has a wide range of effects on several organs and tissues. In recent years, it has become well established that nitric oxide plays a crucial role in the haemodynamic abnormalities that develop in portal hypertension. Several studies have demonstrated increased sermn levels of nitric oxide in patients with portal hypertension. However, correlations and balance between nitric oxide and endothelin have not been studied before in portal hypertensive patients.